| Literature DB >> 17971303 |
Yoshio Terada1, Seiji Inoshita, Hitoshi Kuwana, Takahiko Kobayashi, Tomokazu Okado, Hidenori Ichijo, Sei Sasaki.
Abstract
We investigated the role of apoptosis signal-regulating kinase 1 (ASK1) in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). Blood urea nitrogen (BUN) and serum creatinine were significantly higher in ASK1+/+ mice than in ASK1-/- mice after I/R injury. Renal histology of ASK1+/+ mice showed significantly greater tubular necrosis and degradation. In ASK1-/- mice, phosphorylation of ASK1, JNK, and p38K, and the number of TUNEL-positive cells and infiltrated leukocytes decreased after I/R injury. Apoptotic changes were significantly decreased in cultured renal tubular epithelial cells (TECs) from ASK1-/- mice under hypoxic condition. Transfection with dominant-active ASK1 induced apoptosis in TECs. Protein expression of monocyte chemoattractant protein-1 (MCP-1) was significantly weaker in ASK1-/- mice after I/R injury. Transfection with dominant negative-ASK1 significantly decreased MCP-1 production in TECs. These results demonstrated that ASK1 is activated in I/R-induced AKI, and blockage of ASK1 attenuates renal tubular apoptosis, MCP-1 expression, and renal function.Entities:
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Year: 2007 PMID： 17971303 DOI： 10.1016/j.bbrc.2007.10.122
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575